Obstructive sleep apnea is a major problem in the elderly due to its high prevalence and its well recognized neurocognitive and cardiovascular complications. Afflicted individuals have substantial daytime symptoms including fatigue, malaise, sleepiness and reduced quality of life. Despite this, minimal research has been performed to investigate the mechanisms underlying the development of this disease with aging. Current theory suggests that sleep apnea pathogenesis involves a complex interactions of anatomical variables, protective reflex mechanisms, ventilatory control abnormalities among others. The principal investigator proposes to extend the observations from his Beeson award to pursue more comprehensive evaluations of the critical variables using a new patient population in both sleep and wakefulness. During the proposed granting period, we will investigate the normal effects of aging on a number of mechanistic variables of interest and further we will define the impact of sleep apnea disease on these parameters. Based on our preliminary data, the groups of variables will likely form phenotypic clusters whereby a certain abnormality (or group of abnormalities) either causes disease (or protects from disease) in older and younger individuals. This protocol will allow us to test a number of hypotheses regarding potential mechanisms underlying sleep apnea using state-of-the-art technology and methods. We have developed a conceptual framework whereby we can classify patients into OSA or control based on their underlying pathophysiology with a view towards understand why a given patient does or does not have sleep apnea. Ultimately our goal is to identify new therapeutic targets for sleep apnea in the elderly since the current therapies are often poorly tolerated in this and other age groups. PUBLIC HEALTH RELEVANCE: Sleep apnea is a major problem for the elderly because it is very common and leads to marked reductions in quality of life. Treatments for sleep apnea are often poorly tolerated by older individuals and therefore research into underlying mechanisms is very important in order for new treatments to be developed. We plan to characterize many of the variables important in causing sleep apnea so that we can develop a better understanding of why the elderly develop this disease, and how best to prevent or minimize its complications.